The purpose of this project is to identify the determinants of non- insulin-dependent diabetes (NIDDM), various types of arthritis, and gallbladder disease, and elucidate the natural history of the diseases. Genetic and environmental risk factors for NIDDM have been studied in the Pima Indians. The residents of the study area, approximately 5000 people, have participated in a longitudinal population study since 1965, allowing observations of the natural history of diabetes mellitus. Risk factors for obesity, hypertension, and cholelithiasis are also studied, along with the relationships of these diseases to diabetes and their effects on mortality rates. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. The roles of obesity, serum insulin concentrations, impaired glucose tolerance, occupational and leisure-time physical activity and diabetes in relatives are assessed.